1. Field of the Invention
The present invention relates to a liposome composition and a method for producing the same. The present invention relates to a liposome composition which can be preferably used for pharmaceutical applications and a method for producing the same.
2. Description of the Related Art
A liposome (hereinafter, also referred to as lipid vesicle) is a closed vesicle formed of a lipid bilayer membrane using lipids, and has a water phase (inner water phase) within the space of the closed vesicle. Liposomes are usually present in a state of being dispersed in an aqueous solution (outer water phase) outside the closed vesicle.
Liposomes have been studied for a variety of applications such as immune sensors, artificial red blood cells, and carriers of drug delivery systems taking advantage of features such as barrier capacity, compound retention capacity, biocompatibility, the degree of freedom of setting the particle size, ready biodegradability, and surface-modifying properties. In carrier applications, liposomes can encapsulate water-soluble compounds, lipophilic low-molecular weight materials, polymers and a wide range of materials.
In the case where liposomes are used particularly as a carrier for a drug delivery system, it is necessary to make a particle size to be about 200 nm or less in terms of permeation through a biological membrane. Further, in a carrier for a drug delivery system, it is also necessary to have liposomes which form particles having a good dispersibility under the temperature conditions of about 37° C. which is the body temperature of a mammal. In particular, with regard to nano-sized fine particles, it is preferred to impart preservation stability from various viewpoints such as aggregation, precipitation, and leakage of drugs.
As a carrier for a drug delivery system, in the case where a drug (solution or the like containing liposomes containing a drug) is administered by intravenous injection, high safety is required for an intravenous injection product. Additives such as chlorinated solvents, for example chloroform, or a dispersant (hereinafter, the dispersant also includes a dispersing aid or the like) whose use are not allowed are undesirable. In addition, impartment of stability to a pharmaceutical product is also necessary, and correspondingly suppression of drug leakage, lipid decomposition or the like after storage is required. Further, suitability for sterile filtration is also required in order to guarantee sterility. When it is desired to produce liposomes as a pharmaceutical product on an industrial scale, it is necessary to take into account the requirements as described above.
In a drug delivery system, a liposome composition containing a pharmaceutical (drug) is required to deliver the pharmaceutical into an affected area and then release a required amount of the drug therein. However, achieving both easy release and preservation stability of a drug in a liposome composition is a contradictory problem. Therefore, there is a need for achieving both of them.
JP2013-022482A discloses a method for producing a liposome by an emulsification method without passing through a drying and solidifying step of a lipid membrane. Disclosed therein is a method for producing a liposome, using a water-soluble emulsifier which does not destroy a liposome lipid membrane, as an emulsifier, specifically Pluronic as a nonionic surfactant. Generally, surfactants significantly affect the strength of the liposome membrane, which will therefore require improving.
JP1994-009374A (JP-H06-009374A) discloses a liposome composition formed by encapsulating a drug-containing liquid 2.0 to 5.0-fold hyper-osmotic with respect to an osmotic pressure of a biological fluid of a warm-blooded animal, within a liposome which is a small unilamellar vesicle having a membrane phase transition temperature of 40° C. to 45° C. In addition, it is also disclosed that this liposome composition is a liposome composition obtained through a drying and solidifying step of the mixed lipid membrane. By rendering the conditions of the lipid membrane 2.0 to 5.0-fold hyper-osmotic with respect to an osmotic pressure of a biological fluid of a warm-blooded animal, this liposome composition has properties by which the release of a drug is suppressed at a low temperature and the drug is released all at once at a high temperature, for the purpose of hyperthermia. Because the release suppression at a low temperature has a short time duration of less than a few tens of minutes, and there is weakness in the lipid membrane that has undergone the drying and solidifying step of the mixed lipid membrane, no reference is made to preservation stability over an extended period of time or release control on the order of several tens of hours.
In all of the above-mentioned documents, a liposome composition having a practically required long-term preservation stability and also having a release rate of a drug on the order of several tells of hours and a method for producing the same have not been fully established, and correspondingly improvements are desired.